This invention relates to the diagnosis and treatment of HIV-1 infections.
Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immunodeficiency syndrome (AIDS), Broder et al. (1984) N. Engl. J. Med. 311:1292-1297 and Barre-Sinoussi et al. (1983) Science 220:868-870. Depletion of the CD4.sup.+ lymphocyte population is believed to account for most of the severe immunologic abnormalities seen in AIDS patients, Fauci et al. (1984) Ann. Int. Med. 100:92-106. Depletion occurs prior to, or coincident with, development of the severe opportunistic infections seen in most HIV-1-infected individuals, Gottlieb et al. (1981) N. Eng. J. Med. 305:1425-1431, Lane et al. (1985) Am. J. Med. 78:417-422, and Friedman-Kien et al. (1982) Ann. Int. Med. 96:693-699.
Antibodies that react with allogenic T lymphocytes have been detected in the serum of HIV-1 seropositive individuals, Pollack et al. (1983) in Non-HLA Antigens in Health, Aging, and Malignancy, (Alan R. Liss, New York) pp. 209-213, Kloster et al. (1984) Clin. Immunol. Immunopath 30:330-335, Pruzanski et al. (1984) Aids Res. 1:211-220, Kiprov et al. (1985) N. Engl. J. Med. 312:1517, Dorsett et al. (1985) Am. J. Med. 78:621-626, Tomar et al. (1985) Clin. Immunol. Immunopath 37:37-47, Stricker et al. (1987) Nature 327:710-713, and Otzurk et al. (1987) J. Clin. Immunol. 7:130-139.Recently, serum antibodies that bind to soluble, recombinant forms of the cell surface protein CD4 were detected in 9-13% of individuals infected by HIV-1, Chams et al. (1988) AIDS 2:353-361, Thiriart et al. (1988) AIDS 2:345-351, and Kowalski et al. (1989) Proc. Natl. Acad. Sci. USA 86:3346-3350, but the ability of such antibodies to bind to native CD4 could not be demonstrated, Chams et al. (1988), AIDS 2:353-361.
CD43, also known as leukosialin, sialophorin, gpL115, and LSCP, is a major lymphocyte surface sialoglycoprotein expressed by essentially all leukocytes, Borche et al. (1987) Eur. J. Immunol. 17:1523-1526. The binding of antibodies to CD43 can activate T lymphocytes, Mentzer et al (1987) S. Exp. Med. 165:1383-1392, Axelsson (1988) J. Immunol. 141:2912-2917, bypassing the T cell receptor/CD3 complex, Silverman et al. (1989) J. Immunol. 142:4194-4200. CD43 expression is diminished or abnormal on lymphocytes from children with Wiskott Aldrich syndrome, a severe X chromosome-linked immunodeficiency, Remold-O'Donnell et al. (1984) J. Exp. Med. 159:1705-1723. A CD43-like molecule has been found on the surface of brain cells in rats, Losy et al. (1984) J. Neuro cytol. 18:71-76.